Skip Navigation



Nucleic Acids Research Advance Access published online on October 6, 2009
Nucleic Acids Research, doi:10.1093/nar/gkp768
This Article
Right arrow Full Text Freely available
Right arrow Print PDF (2949K) Freely available
Right arrow Screen PDF (461K) Freely available
Right arrow Supplementary Data
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Commercial Re-use Guidelines
for Open Access NAR Content
Google Scholar
Right arrow Articles by Liu, S.
Right arrow Articles by Wang, Y.
PubMed
Right arrow PubMed Citation
Right arrow Articles by Liu, S.
Right arrow Articles by Wang, Y.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author(s) 2009. Published by Oxford University Press.
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.5/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Genome Integrity, Repair and Replication

MEPE/OF45 protects cells from DNA damage induced killing via stabilizing CHK1

Shuang Liu1,2, Hongyan Wang2, Xiang Wang3, Lin Lu3, Ning Gao1, Peter S. N. Rowe4, Baocheng Hu1,2,* and Ya Wang2,*

1Beijing Institute of Biotechnology, Beijing 100850, China, 2Department of Radiation Oncology, Winship Cancer Institute, Emory University, Atlanta, GA 30322, USA, 3Department of Radiation Oncology, Thomas Jefferson University, Philadelphia, PA 19107 and 4Department of Internal Medicine, Kidney Institute & Division of Nephrology, University of Kansas Medical Center, Kansas City, KS 66160, USA

*To whom correspondence should be addressed. Tel: +1 404 778 1832; Fax: +1 404 778 1750; Email: yawang{at}radonc.emory.org

Correspondence may also be addressed to Baocheng Hu. Tel/Fax: +8610 6824 8045; Email: baochenghu{at}yahoo.com.cn

Received June 17, 2009. Revised August 30, 2009. Accepted September 1, 2009.

Matrix extracellular phosphoglycoprotein/osteoblast factor 45 (MEPE/OF45) was cloned in 2000 with functions related to bone metabolism. We identified MEPE/OF45 for the first time as a new co-factor of CHK1 in mammalian cells to protect cells from DNA damage induced killing. We demonstrate here that MEPE/OF45 directly interacts with CHK1. Knocking down MEPE/OF45 decreases CHK1 levels and sensitizes the cells to DNA damage inducers such as ionizing radiation (IR) or camptothicin (CPT)-induced killing. Over-expressing wild-type MEPE/OF45, but not the mutant MEPE/OF45 (depleted the key domain to interact with CHK1) increases CHK1 levels in the cells and increases the resistance of the cells to IR or CPT. MEPE/OF45, interacting with CHK1, increases CHK1 half-life and decreases CHK1 degradation through the ubiquitine-mediated pathway. In addition, the interaction of MEPE/OF45 with CHK1 decreases CHK1 levels in the ubiquitin E3 ligases (Cul1 and Cul4A) complex, which suggests that MEPE/OF45 competes with the ubiquitin E3 ligases binding to CHK1 and thus decreases CHK1 from ubiquitin-mediated proteolysis. These findings reveal an important role of MEPE/OF45 in protecting cells from DNA damage induced killing through stabilizing CHK1, which would provide MEPE/OF45 as a new target for sensitizing tumor cells to radiotherapy or chemotherapy.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?




Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.